Abstract Brain-computer interfaces (BCI) offer hope to treat otherwise intractable neurological disease. However, the current state of BCI is still short of the potential; solutions to fundamental biological and engineering problems must be found before BCIs can be broadly used for patient care. A collaborative group at UCSD has developed a high-density array of microelectrodes (microgrid) that surmounts many of the major hurdles facing neural interface devices. Our devices are thin, non-destructive, and rest lightly on the surface of the brain, and they are tightly packed with sensors to create an extremely high-resolution interface. The goal of this proposal is to study cortical physiology using our high-density microgrids. The first experiments will test the capabilities of these surface microgrids for discriminating cortical columns in the rat ?barrel cortex,? a region within somatosensory cortex where mechanical whisker stimulation evokes neuronal activity. Barrel cortex contains a 1:1 mapping of whiskers to cortical columns, and the columns have well demarcated borders. The patterns of evoked and spontaneous activity in barrel cortex will be recorded from the pial surface using our microgrids, and the spectral and spatial patterns of activity will be compared to similar recordings from human cortex during awake and anesthetized brain surgeries. The results of these studies will define the spatial boundaries of human cortical columns. In the second set of experiments, in rat somatosensory cortex I will record laminar neuronal activity using a high-density depth probe while electrically stimulating the cortical surface. This experiment will show how surface stimulation affects neuronal activity, layer-by-layer. The results from the animal studies will then be followed by similar experiments in human, where stimulation will be performed through a surface microgrid while simultaneously recording neural activity from nearby contacts on the same surface microgrid. The results from the first experiments will define the functional spatial boundaries of human cortical columns and aid in optimizing microgrid design for minimal electrode redundancy. The results of the second experiments will define the local neuronal effects of surface stimulation. Together, these experiments will aid in developing new treatments for some of the most debilitating neurological diseases.